Traumatic central cord syndrome: neurological and functional outcome at 3 years.

STUDY DESIGN: Retrospective cohort analysis with prospective follow-up. OBJECTIVES: To evaluate neurological and functional recovery following central cord syndrome. SETTING: Northern Ireland, population 1.8 million. METHODS: Twenty-seven cords were identified in 1 year. Five managed conservatively and 22 with surgery. American Spinal Injury Association (ASIA) motor scores (AMS) were calculated to assess neurological recovery. Rotterdam scores assessed functional independence at 3 years. RESULTS: Average age was 62 years. Mechanism of injury was a fall with neck hyperextension in 81% patients. Average AMS in surgical patients improved from injury, preoperatively, postoperatively, 6 months and 3 years from 51, 81, 83, 90 to 96, respectively. Conservative patients improved from time of injury to day 10 from 57 to 86 and then fell to 84 at 6 months. By 3 years, this had recovered to 91. There was no statistical significant difference in AMS (P=0.15)/change in AMS (ΔAMS) (P=0.92) or percentage of motor deficit resolution (P=0.23) between groups at 3 years. Two patients underwent surgery within 48 h and achieved full motor recovery by 3 years, but this was not significant (P=0.2). ASIA score improvement had a positive correlation with age at injury. Patients treated with surgery had better Rotterdam scores at 3 years than those managed conservatively (P=0.05). CONCLUSIONS: This study confirms the natural history of central cord syndrome. Although it demonstrates equivocal neurological recovery for both groups, patients treated with surgery regained a greater degree of functional independence.

Paired pulse depression in the somatosensory cortex: associations between MEG and BOLD fMRI.

Interpretation of the blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) requires an understanding of the underlying neuronal activity. Here we report on a study using both magnetoencephalography (MEG) and BOLD fMRI, to measure the brain's functional response to electrical stimulation of the median nerve in a paired pulse paradigm. Interstimulus Intervals (ISIs) of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 s are used to investigate how the MEG detected neural response to a second pulse is affected by that from a preceding pulse and if these MEG modulations are reflected in the BOLD response. We focus on neural oscillatory activity in the ß-band (13-30 Hz) and the P35m component of the signal averaged evoked response in the sensorimotor cortex. A spatial separation of ß ERD and ERS following each pulse is demonstrated suggesting that these two effects arise from separate neural generators, with ERS exhibiting a closer spatial relationship with the BOLD response. The spatial distribution and extent of BOLD activity were unaffected by ISI, but modulations in peak amplitude and latency were observed. Non-linearities in both induced oscillatory activity ERS and in the signal averaged evoked response are found for ISIs of up to 2s when the signal averaged evoked response has returned to baseline, with the P35m component displaying paired pulse depression effects. The ß-band ERS magnitude was modulated by ISI, however the ERD magnitude was not. These results support the assumption that BOLD non-linearity arises not only from a non-linear vascular response to neural activity but also a non-linear neural response to the stimulus with ISI up to 2 s.

Contrasting nutrient effects on the plasma levels of an amino acid-like antiepileptic agent from jejunal administration in dogs.

The absorption of gabapentin was investigated by monitoring drug plasma levels as a function of time following midjejunal administration in mongrel dogs. From previous work, dose-dependent absorption had been postulated to be a consequence of carrier-mediated transport and a paracellular pathway had been postulated to contribute to the passive absorption component in mammalian small intestine. The potential for amino acid inhibition of the carrier-mediated absorption component was investigated by drug coinfusion with leucine and phenylalanine. The potential for monosaccharide-enhanced increases in drug absorption was studied by drug coinfusion with D-glucose and 3-O-methylglucose. While lower drug plasma levels were observed with amino acid coinfusion versus controls in each of the dogs studied, mean area under the plasma level time curves (AUC) were not statistically significantly different (p < or = 0.07). Monosaccharide coinfusion significantly increased gabapentin AUC over control studies (p < or = 0.014) and over coinfusion with L-system amino acids (p < or = 0.0025). Implications for the mechanisms of intestinal absorption of this amino acid-like antiepileptic drug in this canine model are discussed.

fMRI and MEG analysis of visceral pain in healthy volunteers.

BACKGROUND: Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis. METHODS: Liminal and painful rectal barostat balloon inflation thresholds were assessed in 14 female healthy volunteers. Subliminal, liminal and painful 40s periods of distension were applied in a pseudo-randomized paradigm during fMRI and MEG neuroimaging. Functional MRI data analysis was performed comparing standard box-car models of the full 40s of stimulus (Block) with models of the inflation (Ramp-On) and deflation (Ramp-Off) of the barostat. Similar models were used in MEG analysis of oscillatory activity. KEY RESULTS: Modeling the data using a standard Block analysis failed to detect areas of interest found to be active using Ramp-On and Ramp-Off models. Ramp-On generated activity in anterior insula and cingulate regions and other pain-matrix associated areas. Ramp-Off demonstrated activity of a network of posterior insula, SII and posterior cingulate. Active areas were consistent with those identified from MEG data. CONCLUSIONS & INFERENCES: In studies of visceral pain, fMRI model design strongly influences the detected activity and must be accounted for to effectively explore the fMRI data in healthy subjects and within patient groups. In particular a strong cortical response is detected to inflation and deflation of the barostat, rather than to its absolute volume.

Restricting a familiar name in response to learning a new one: evidence for the mutual exclusivity bias in young two-year-olds.

Children under 2 1/2 years old tend to interpret novel words in accordance with the Mutual Exclusivity Principle, but tend not to reinterpret familiar words this way. Because alternative principles have been proposed that only predict the novel word effects, and because tests of the familiar word effects may have been flawed, a new test was administered. In Experiment 1 (N = 32), 24- to 25-month-olds heard stories in which a novel noun was used for an atypical exemplar of a familiar noun. When asked to select exemplars of the familiar noun, they showed a small but reliable tendency to avoid the object from the story. In Experiment 2 (N = 16), the novel nouns in the stories were replaced by pronouns and proper names, and the children did not avoid the story object in the test of the familiar noun. Thus, the aversion to this object that was observed in Experiment 1 was not due to its greater exposure or its being referenced immediately before testing, but to toddlers' Mutual Exclusivity bias. Their bias is hypothesized to be a form of implicit probabilistic knowledge that derives from the competitive nature of category retrieval.

Colonic absorption of antiepileptic agents.

PURPOSE: To evaluate a canine intestinal accessport model to study colonic absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen to study absorption of a lipophilic and hydrophilic compound, respectively. METHODS: Drug plasma level-time plots were generated subsequent to small intestinal and colonic drug administration of both drugs. The poorly water-soluble phenytoin was administered in two doses to evaluate the impact of dissolution rate limits on colonic absorption. Maximal plasma concentration (Cmax) and area under the plasma level-time curve (AUC) were used to assess the relative contribution of colonic absorption to plasma levels. RESULTS: Whereas colonic gabapentin AUC and Cmax were only 0.25 and 0.15 of those seen after small intestinal administration, colonic phenytoin AUC and Cmax were one half and equivalent to, respectively, those observed for small intestinal administration. Furthermore, colonic administration of a higher phenytoin dose showed secondary maxima and continued increases in drug plasma levels with time. CONCLUSIONS: Colonic gabapentin absorption is poor compared with upper intestinal absorption, consistent with membrane transport rate limits to the absorption of this hydrophilic AED. Peak phenytoin plasma levels from colonic and small intestinal administration are comparable, indicating membrane transport does not limit absorption of this lipophilic agent. Continued plasma-level increases from higher phenytoin doses are consistent with dissolution-rate control of drug absorption in the colon. We suggest that colonic absorption provides a greater potential for toxicity from phenytoin overdose as a function of continued drug dissolution than for gabapentin overdose.

Serum immunoglobulin levels in hepatitis-B antigen-positive and hepatitis-B antigen-negative acute hepatitis.

IgG, IgA and IgM levels were measured in the serum of 73 patients with hepatitis-B antigen-positive (virus-B) acute hepatitis and 48 patients with hepatitis-B antigen-negative (virus-A) hepatitis. The mean serum IgM level on admission was significantly higher in virus-A than in virus-B hepatitis (p less than 0,01), and remained so for 2-3 weeks. However, the overlap between the individual figures in the two forms of the disease was so great as to make the estimation of little diagnostic value. The mean serum IgG and IgA levels at the time of admission were not significantly different in the patients with and without hepatitis-B anti-genaemia.

Emergence of multiply resistant pneumococci.

Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.